Studies on the mechanism of neutralization of poliovirus by antibody have indicated that antibody converts and stabilized the protein coat in a conformational state that renders the particle non- infectious. Although the virus-antibody complex is able to adsorb to susceptible cells, it is unable to uncoat, thereby aborting the replication cycle at the uncoating stage. Further studies are in progress to support and extend these tentative conclusions. Studies on the mechanism of uncoating have recently been initiated. A subcellular fraction from susceptible cells have been obtained that is capable of uncoating poliovirus in a cell-free, in vitro system. The uncoating reaction in vitro (and presumably in vivo) appears to be a 2- stage phenomenon: the isolated factor induces a change in the viral protein coat that renders it sensitive to various proteases. Successive treatment of virus with the uncoating factor and a protease, alters the virion in a manner that exposes the viral RNA, as indicated by its sensitivity to RNase. Studies are in progress to (1) purify and characterize the uncoating factor; (2) to determine the requirements and optimal conditions of the uncoating reaction; (3) to characterize the reaction mechanism and reaction products.